FDA issued a complete response letter (CRL) to AstraZeneca seeking additional clinical data for benralizumab, sold as Fasenra, in the treatment of patients with inadequately controlled chronic rhinosinusitis with nasal polyps.
AstraZeneca announced this week that the FDA issued a complete response letter (CRL) regarding its supplemental Biologics License Application (sBLA) for benralizumab, sold as Fasenra, in the treatment of patients with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP).
The sBLA was based on data from the OSTRO phase 3 trial, which evaluated the efficacy and safety of benralizumab compared with placebo in patients with CRSwNP. Benralizumab was evaluated in patients, regardless of blood eosinophil count, with or without asthma, who were symptomatic despite standard of care therapy.
The biologic met both co–primary end points, nasal polyp burden and patient-reported nasal blockage, with a safety profile consistent with the known profile of the medicine. The CRL requested additional clinical data that AstraZeneca said it is currently working to address with the FDA.
Designed as an interleukin (IL)-5 monoclonal antibody that depletes eosinophils through antibody-dependent cell-mediated cytotoxicity, benralizumab is currently approved as an add-on maintenance treatment for severe eosinophilic asthma and for self-administration in the United States.
The IL-5 inhibitor was granted an Orphan Drug Designation (ODD) for eosinophilic granulomatosis with polyangiitis in 2018, and hypereosinophilic syndrome and eosinophilic esophagitis (EoE) in 2019. The FDA also granted an ODD for benralizumab in the treatment of eosinophilic gastroenteritis (EGE) and eosinophilic gastritis (EG) in November 2021, and a Fast Track Designation for the treatment of EG with or without EGE in the United States.
In the management of CRSwNP, biologics currently serve as an option for those with uncontrolled severe disease who are unresponsive to standard of care topical corticosteriods and nasal saline, either as a monotherapy or in combination with other available treatment.
The first FDA-approved biologic for CRSwNP, dupilumab, has been associated with significant improvements of health-related quality of life and general health status in the treatment of patients with severe CRSwNP.
Dupilumab is a fully human monoclonal antibody against the IL-4 receptor α-subunit (IL-4Rα) that inhibits IL-4 and IL-13 signaling. It also has been shown to significantly reduce anosmia prevalence, which affects 60% to 80% of patients with CRSwNP and is linked with physical and social alterations that impair quality of life.
Mepolizumab, a targeted, humanized anti–IL-5 monoclonal antibody, is the second biologic approved by the FDA for the treatment of CRSwNP.
Endoscopic sinus surgery (ESS) has additionally been implemented to control CRSwNP symptom burden, but recurrence of nasal polyps has been reported to occur in approximately 60% to 70% of patients after 18 months. Comorbidities have also been shown to further increase risk of nasal polyp recurrence in those who have undergone ESS.